tbuckley/cabot-search huggingface dataset:
Abstract B021: The axon guidance receptor UNC5B is a driver of pancreatic cancer metastasis
Authors: Chris Harris, Anthony Casabianca, Zach Sechrist, Cory Shields, Wade Narrow, Tracy Withers, Crissy Dudgeon, Mike O'Dell, Aram Hezel, Darren Carpizo
Journal: Cancer Research (2022)

Abstract Axon guidance pathways have often been linked to tumorigenesis by informatics analyses, but their roles in tumorigenesis are not well understood at a functional level. Here we show that axon guidance receptor UNC5B and its ligand, NTN1, promote the metastasis of pancreatic ductal adenocarcinomas (PDACs) by reducing anoikis and by promoting a mesenchymal phenotype. In vivo, removal of two floxed UNC5B alleles eliminated PDAC metastasis in the genetically engineered KPC mouse model, and also reduced metastasis by xenografted PDAC cell lines. PDAC metastasis also decreased upon treatment of animals with NP137, an antibody that targets NTN1. In vitro, deletion of UNC5B from pancreatic adenocarcinoma cell lines reduced invasiveness, and was sufficient to convert PDAC cell lines from an epithelial to a mesenchymal state. UNC5B also increased YAP1 expression but decreased anoikis; anoikis could then be restored by treatment with the YAP1 inhibitor CA3. Clinically, UNC5B expression associated with poor outcomes in patients with pancreatic adenocarcinomas. UNC5B and NTN1 expression increased upon truncation of the SWI/SNF component ARID1A, which is recurrently mutated in PDACs. Highly focal amplifications of UNC5B were also observed in some patient samples, and were mutually exclusive with mutations in ARID1A or ARID1B. NP137 is currently in clinical trials for various cancers, and may benefit pancreatic adenocarcinoma patients, particularly those with UNC5B amplifications or with ARID1A/ARID1B mutations. Citation Format: Chris Harris, Anthony Casabianca, Zach Sechrist, Cory Shields, Wade Narrow, Tracy Withers, Crissy Dudgeon, Mike O'Dell, Aram Hezel, Darren Carpizo. The axon guidance receptor UNC5B is a driver of pancreatic cancer metastasis [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B021.
Abstract A074: Developing a novel in vivo model of pancreatic ductal adenocarcinoma using primary tumor samples and humanised mouse models
Authors: Alexander J. P. Fulton, Kourosh Saeb-Parsy, Bristi Basu
Journal: Cancer Research (2022)

Abstract Pancreatic cancer (PDAC) remains one of the most lethal malignancies due to its late diagnosis and poor response to treatment. Preclinical models reflecting the uniquely complex structure of PDAC cells and the surrounding tumor microenvironment (TME) are required to ensure translational results. PDAC organoids, ex vivo 3D models of primary tumor cells, form an exciting preclinical model that reflects the complexity of PDAC. Tumor organoids co-cultured with stromal and immune cells have been previously explored in vitro but have thus far remained limited in any in vivo capacity. We therefore aimed to establish and characterize in vitro co-cultured PDAC organoids using primary human PDAC tumor samples plus autologous peripheral or splenic lymphocytes. Subsequent preliminary in vivo models have been established by engrafting co-cultured PDAC organoids and PDAC cancer associated fibroblasts into immunocompromised mice. The pilot data assessed retention, growth kinetics and metastatic potential and will subsequently form the foundation for comparable experiments using autologous humanized mouse models. This humanized mouse model, consisting of autologous human malignant, stromal and immune compartments, will add to the existing repertoire of preclinical models by more closely representing the entire tumor volume. In vitro and in vivo data compared to other preclinical models. Additional preliminary therapeutic response data may provide translational value and warrant further evaluation. Citation Format: Alexander J. P. Fulton, Kourosh Saeb-Parsy, Bristi Basu. Developing a novel in vivo model of pancreatic ductal adenocarcinoma using primary tumor samples and humanised mouse models [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A074.
Abstract C019: FAK suppresses antigen processing and presentation to promote immune evasion in pancreatic cancer
Authors: Marta Canel, Aleksandra Slawinska, David W. Lonergan, Ashwin A. Kallor, Rosie Upstill-Goddard, Catherine Davidson, Alex von Kriegsheim, Andrew V. Biankin, Adam Bryron, Javier Alfaro, Alan Serrels
Journal: Cancer Research (2022)

Abstract Immunotherapy for the treatment of Pancreatic Ductal Adenocarcinoma (PDAC) has shown limited efficacy. Poor CD8 T-cell infiltration, low neoantigen load and a highly immunosuppressive tumor microenvironment are key factors that contribute to this lack of response. Here, we identify a novel role for Focal Adhesion Kinase (FAK) in regulating type-II interferon signalling in human and murine PDAC cells and tumors, leading to suppression of antigen processing and presentation pathways critical for T-cell tumor recognition. We find that FAK loss promotes expression of the immunoproteasome and MHC-I, resulting in a significant increase in the diversity of antigens presented by FAK-/- PDAC cells. We show that regulation of the immunoproteasome subunit Psmb8 (β5i) is a critical determinant of this response, optimising the physicochemical properties of the peptide repertoire for high-affinity binding to MHC-I. Expression of the immunoproteasome and MHC-I can be further amplified in a STAT1-dependent manner via co-depletion of FAK and STAT3, leading to extensive CD8 T-cell infiltration into PDAC tumors and further restraint of tumor growth. Regulation of antigen processing and presentation by FAK preferentially occurs in human and murine PDAC cells and tumors of the classical/progenitor molecular subtype, further suggesting that precision medicine approaches based on molecular subtyping should be integrated into current and future clinical testing of FAK targeted therapies for the treatment of pancreatic cancer. Citation Format: Marta Canel, Aleksandra Slawinska, David W. Lonergan, Ashwin A. Kallor, Rosie Upstill-Goddard, Catherine Davidson, Alex von Kriegsheim, Andrew V. Biankin, Adam Bryron, Javier Alfaro, Alan Serrels. FAK suppresses antigen processing and presentation to promote immune evasion in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr C019.
Abstract B027: Three-dimensional genomic analysis of human pancreatic intraepithelial neoplasia (PanIN) reveals striking multifocality and genetic heterogeneity
Authors: Alicia M. Braxton, Ashley Kiemen, Rachel Karchin, Yuchen Jiao, Pei-Hsun Wu, Ralph H Hruban, Denis Wirtz, Laura D. Wood
Journal: Cancer Research (2022)

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Short Talks from Proffered Abstracts section (PR007) of the Conference Proceedings. Citation Format: Alicia M. Braxton, Ashley Kiemen, Rachel Karchin, Yuchen Jiao, Pei-Hsun Wu, Ralph H Hruban, Denis Wirtz, Laura D. Wood. Three-dimensional genomic analysis of human pancreatic intraepithelial neoplasia (PanIN) reveals striking multifocality and genetic heterogeneity [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B027.
Abstract A078: Inhibition of precancerous transformation via drug-induced p53 activation
Authors: Jennifer J. Twardowski, Thomas I. Heist, Stephano S. Mello
Journal: Cancer Research (2022)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer deaths in the US and has a 5-year survival rate of less than 10%. This low survival rate is largely due to low rates of early detection and the lack of treatments capable of inhibiting disease progression. Risk factors for PDAC include smoking, alcohol abuse, and pancreatitis. Pancreatic injury associated with pancreatitis is characterized by inflammation, fibrosis, and acinar cell death. Surviving acinar cells undergo acinar-to-ductal metaplasia (ADM), a regenerative process in which cells dedifferentiate, proliferate, and then redifferentiate into acinar cells. Recurrent pancreatic injury can sustain ADM and preclude redifferentiation, resulting in exocrine insufficiency and the formation of precursor lesions known as pancreatic intraepithelial neoplasia (PanIN). PanIN lesions harbor activating mutations in the MAP kinase pathway protein Kras, and can transform into PDAC after acquiring inactivating mutations in tumor suppressor p53. The lack of treatment options for pancreatitis patients reinforces the need for strategies that could resolve pancreatic damage and stop disease progression. Towards this end, we have recently shown that drug-induced activation of p53 in mouse models of pancreatitis preserves acinar cells, reduces the proliferation of PanIN lesions, and lowers levels of MAP kinase phosphorylation. We have also observed p53 activation during embryonic development of the pancreas, specifically in exocrine progenitor cells that commit to the acinar fate, suggesting a novel role of p53 in pancreatic differentiation. Based on our findings, we hypothesize that p53 activation can signal for the differentiation of acinar cells, and restrain PanIN proliferation through the suppression of MAP kinase signaling. Our studies will define the role of p53 in pancreatic differentiation and the potential of pharmacological p53 activation for the treatment for pancreatitis and prevention of PDAC. Citation Format: Jennifer J. Twardowski, Thomas I. Heist, Stephano S. Mello. Inhibition of precancerous transformation via drug-induced p53 activation [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A078.
Abstract IA014: Collagen cleavage controls PDAC metabolism and malignancy via a DDR1-NRF2 cascade and mitochondrial biogenesis
Authors: Michael Karin, Hua Su
Journal: Cancer Research (2022)

Abstract PDAC is distinct by being highly desmoplastic, due to the activation and eventual infiltration of cancer associated fibroblasts (CAF) and the extracellular matrix (ECM) they produce, which is mainly composed of collagen type I (Col I). The role of fibroblasts and collagen in PDAC pathology is highly contentious, ranging from tumor stimulatory to tumor inhibitory. Using mouse models and human specimens we found that the way in which Col I affects PDAC progression, metabolism and its response to therapy is highly dependent on its cleavage by matrix metalloproteases (MMP). Whereas noncleaved Col I inhibits PDAC metabolism, inhibits human and mouse PDAC growth in mice and is correlated with improved survival after surgical resection, MMP generated Col I fragments stimulate tumor metabolism and growth and correlate with poor post-resection survival. These differential activities of cleaved and noncleaved Col I depend on its interactions with the receptor tyrosine kinase DDR1. Whereas MMP-generated Col I binds DDR1 and activates it, intact Col I induces DDR1 degradation. By activating DDR1, cleaved Col I triggers an NF-kB-p62-NRF2 signaling cascade, whose major efferent, NRF2, controls many aspects of PDAC metabolism, including macropinocytosis, aerobic glycolysis, respiration and mitochondrial biogenesis. Inhibitors of NRF2 and mitochondrial biogenesis induce regression of established PDAC in-vivo and compromise its growth and survival in-vitro. Citation Format: Michael Karin, Hua Su. Collagen cleavage controls PDAC metabolism and malignancy via a DDR1-NRF2 cascade and mitochondrial biogenesis [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr IA014.
A unifying force for the realization of medical AI
Authors: Jochen K. Lennerz, Ursula Green, Drew F. K. Williamson, Faisal Mahmood
Journal: npj Digital Medicine (2022)

Artificial Intelligence (AI) in medicine has grown rapidly, yet few algorithms have been deployed. It is not the problem with the AI itself but with the way functions and results are communicated. Regulatory science provides the appropriate language and solutions to this problem for three reasons: First, there is value in the intentionally interdisciplinary regulatory language. Second, regulatory concepts are important for AI researchers because these concepts enable tackling of risk and safety concerns as well as understanding of recently proposed regulations in the US and Europe. Third, regulatory science is a scientific discipline that evaluates and challenges current regulation—aiming for evidence-based improvements. Knowledge of the regulatory language, concepts, and science should be regarded a core competency for communicating medical innovation. Regulatory grade communication will be the key to bringing medical AI from hype to standard of care. Foregoing the possible benefits of regulatory science as a unifying force for the realization of medical AI is a missed opportunity.
Balloon catheters versus vaginal prostaglandins for labour induction (CPI Collaborative): an individual participant data meta-analysis of randomised controlled trials
Authors: Madeleine N Jones, Kirsten R Palmer, Maleesa M Pathirana, Jose Guilherme Cecatti, Olimpio B Moraes Filho, Lena Marions, Måns Edlund, Martina Prager, Craig Pennell, Jan E Dickinson, Nelson Sass, Marta Jozwiak, Mieke Ten Eikelder, Katrien Oude Rengerink, Kitty W M Bloemenkamp, Amanda Henry, Ellen C L Løkkegaard, Ib Jarle Christensen, Jeff M Szychowski, Rodney K Edwards, Michael Beckmann, Caroline Diguisto, Amélie Le Gouge, Franck Perrotin, Ian Symonds, Sean O'Leary, Daniel L Rolnik, Ben W Mol, Wentao Li
Journal: The Lancet (2022)
Astrocyte endfoot formation controls the termination of oligodendrocyte precursor cell perivascular migration during development
Authors: Yixun Su, Xiaorui Wang, Yujian Yang, Liang Chen, Wenlong Xia, Kimberly K. Hoi, Hui Li, Qi Wang, Guangdan Yu, Xiaoying Chen, Shouyu Wang, Yuxin Wang, Lan Xiao, Alexei Verkhratsky, Stephen P.J. Fancy, Chenju Yi, Jianqin Niu
Journal: Neuron (2022)

Oligodendrocyte precursor cells (OPCs) undergo an extensive and coordinated migration in the developing CNS, using the pre-formed scaffold of developed blood vessels as their physical substrate for migration. While OPC association with vasculature is critical for dispersal, equally important for permitting differentiation and proper myelination of target axons is their appropriate and timely detachment, but regulation of this process remains unclear. Here we demonstrate a correlation between the developmental formation of astrocytic endfeet on vessels and the termination of OPC perivascular migration. Ex vivo and in vivo live imaging shows that astrocyte endfeet physically displace OPCs from vasculature, and genetic abrogation of endfoot formation hinders both OPC detachment from vessels and subsequent differentiation. Astrocyte-derived semaphorins 3a and 6a act to repel OPCs from blood vessels at the cessation of their perivascular migration and, in so doing, permit subsequent OPC differentiation by insulating them from a maturation inhibitory endothelial niche.
Comparison of Visit Rates Before vs After Telehealth Expansion Among Patients With Mental Health Diagnoses Treated at Federally Qualified Health Centers
Authors: Megan B. Cole, Eun Kyung Lee, Melissa Davoust, Kathleen Carey, June-Ho Kim
Journal: JAMA Network Open (2022)

This cohort study assesses visit rates before and after telehealth expansion to assess whether telehealth availability at federally qualified health centers is associated with visit rates for patients with mental health diagnoses.
Biomimetic nanomedicines for precise atherosclerosis theranostics
Authors: Ying Tao, Xinmiao Lan, Yang Zhang, Chenxing Fu, Lu Liu, Feng Cao, Weisheng Guo
Journal: Acta Pharmaceutica Sinica B (2022)

Atherosclerosis (AS) is a leading cause of the life-threatening cardiovascular disease (CVD), creating an urgent need for efficient, biocompatible therapeutics for diagnosis and treatment. Biomimetic nanomedicines (bNMs) are moving closer to fulfilling this need, pushing back the frontier of nano-based drug delivery systems design. This review seeks to outline how these nanomedicines (NMs) might work to diagnose and treat atherosclerosis, to trace the trajectory of their development to date and in the coming years, and to provide a foundation for further discussion about atherosclerotic theranostics.
New WHO recommendations for the care of preterm or low birthweight infants have the potential to transform maternal and newborn health-care delivery
Authors: Gary L Darmstadt, Nafisa Hamoud Al Jaifi, Shabina Ariff, Rajiv Bahl, Mats Blennow, Vanessa Cavallera, Doris Chou, Roger Chou, Liz Comrie-Thomson, Karen M Edmond, Qi Feng, Lawrence Grummer-Strawn, Patricia Fernandez Riera, Shuchita Gupta, Rizwan Ullah Hassan, Zelee Hill, Ayede Adejumoke Idowu, Carole Kenner, Victoria Nakibuuka Kirabira, Reinhard Klinkott, Socorro De Leon-Mendoza, Silke Mader, Karim Manji, Rhonda Marriott, Monica Morgues, Sushma Nangia, Anayda Portela, Suman Rao, Mohammod Shahidullah, Hoang Thi Tran, Andrew D Weeks, Bogale Worku, Khalid Yunis, Vinod K Paul
Journal: The Lancet (2022)
Improving Screening for Aortic Aneurysm With Data Science
Authors: Philip P. Goodney, Grace Wang
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 1: A Novel Method for Rapid Therapeutic Hypothermia Induction Using Transnasal High-Flow Air
Authors: Harikrishna Tandri, Menekem Zviman, Madhavan R Srinivas, Samuir R Khandker, Henry Halperin, Romergryko G Geocadin, Alfredo Quinones-Hinojosa, Aravindan Kolandaivelu
Journal: Circulation (2012)

Abstract: Early induction of hypothermia improves survival in out of hospital cardiac arrest. We investigated the ability of high flow transnasal ambient dry air to induce hypothermia in porcine su...
Screening for Obstructive Sleep Apnea in Adults
Authors: Daniel J. Gottlieb
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Nicotine Pouch Sales Trends in the US by Volume and Nicotine Concentration Levels From 2019 to 2022
Authors: Anuja Majmundar, Christian Okitondo, Ashley Xue, Samuel Asare, Priti Bandi, Nigar Nargis
Journal: JAMA Network Open (2022)

This cross-sectional study examines the sale of 4 nicotine pouch brands in the contiguous 48 states and Washington, DC.
Understanding Hospital-Level Patterns of Nonoperative Management for Low-risk Thyroid and Kidney Cancer
Authors: Mara Koelker, Marieke Krimphove, Khalid Alkhatib, Junaid Nabi, Lindsay E. Kuo, Stuart R. Lipsitz, Toni K. Choueiri, Steven Lee Chang, Gerard M. Doherty, Adam S. Kibel, Quoc-Dien Trinh, Alexander P. Cole
Journal: JAMA Network Open (2022)

Importance There is a growing trend toward conservative management for certain low-risk cancers. Hospital and health-system factors may play a role in determining how these patients are managed. Objective To explore the contribution of hospitals on patients’ odds of nonoperative management for low-risk cancer. Design, Setting, and Participants In this cross-sectional study, individuals with low-risk papillary thyroid cancer and solitary kidney masses were identified, and those receiving nonoperative management vs surgery were compared. Patients with low-risk thyroid cancer and kidney cancer from 2015 to 2017 eligible for nonoperative management according to National Comprehensive Cancer Network guidelines within the National Cancer Database were included. Data were analyzed from October 2021 to March 2022. Main Outcomes and Measures For each facility, the proportion of these patients who received operative and nonoperative management was calculated. A mixed-effects logistic regression model with a hospital-level random effects term was used to calculate factors associated with nonoperative management. Between-hospital variability was assessed using ranked caterpillar plots. Results There were 19 570 individuals with low-risk thyroid cancer (15 344 women [78.4%]; mean [SD] age, 51.74 [95% CI, 51.39-52.08] years) and 41 403 with kidney cancer (25 253 men [61.0%]; mean [SD] age, 61.93 [95% CI, 61.70-62.17] years). In the group with low-risk thyroid cancer, 2.1% (419 patients) received nonoperative management, and in the group with kidney cancer, 9.5% (3928 patients) received nonoperative management. This varied between hospitals from 1.1% (95% CI, 1.0%-1.1%) in the bottom decile to 10.3% (95% CI, 8.0%-12.4%) in the top decile for low-risk thyroid cancer, and from 4.3% (95% CI, 4.1%-4.4%) in the bottom decile to 24.6% (95% CI, 22.7%-26.5%) in the top decile for small kidney masses. For both cancers, age was associated with increased odds of nonoperative treatment. The hospital-level odds of nonoperative management of thyroid and kidney cancer using unadjusted probabilities (observed proportions) were minimally correlated (Spearman ρ = .33; P &amp;amp;lt; .001). Conclusions and Relevance The findings of this study suggest that although health systems factors may be associated with the tendency to pursue nonoperative management, hospital-level factors may differ when comparing unrelated cancers.